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Updated: Oct 11, 2025
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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
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Heart neurons use clock genes to control myocyte proliferation
Emmanouil Tampakakis1, Harshi Gangrade1, Stephanie Glavaris2
1Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Science Advances
|December 1, 2021
Summary
Sympathetic neurons regulate heart size by controlling clock genes Period1/Period2 (Per1/Per2). Inhibiting these neurons promotes cardiomyocyte proliferation and heart enlargement, offering insights into cardiac regeneration.
Area of Science:
- Cardiovascular biology
- Neurobiology
- Chronobiology
Background:
- Neurons influence organ development and regeneration.
- The specific role of cardiac neurons in heart development and regeneration is not well understood.
Purpose of the Study:
- To investigate the role of sympathetic innervation in heart development and regeneration.
- To elucidate the molecular mechanisms linking cardiac neurons to cardiomyocyte proliferation and heart size regulation.
Main Methods:
- Genetic inhibition of sympathetic innervation in vivo.
- Transcriptomic and protein analyses.
- Pharmacological manipulation of sympathetic activity using norepinephrine.
- Analysis of clock gene expression and cell cycle regulation.
Main Results:
- Sympathetic denervation led to heart enlargement and increased cardiomyocyte number.
- Down-regulation of Period1/Period2 (Per1/Per2) clock genes correlated with increased cell cycle gene expression and cardiomyocyte proliferation.
- Per1/Per2 deletion mimicked the effects of sympathetic deficiency on heart size and proliferation.
- Norepinephrine treatment increased Per1/Per2 expression and suppressed cardiomyocyte proliferation.
- Period1/Period2 negatively regulate myocyte mitosis via the Wee1 kinase pathway.
Conclusions:
- A novel link exists between cardiac neurons and clock genes (Per1/Per2) in controlling cardiomyocyte proliferation and heart size.
- These findings provide mechanistic insights into neuromodulation strategies for cardiac regeneration.
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